Methods and systems for quantitative colorimetric capnometry

ABSTRACT

Quantitative colorimetric carbon dioxide detection and measurement systems are disclosed. The systems can include a gas conduit, a colorimetric indicator adapted to exhibit a color change in response to exposure to carbon dioxide gas, a temperature controller operatively coupled to the colorimetric indicator and configured to control the temperature of the colorimetric indicator, an electro-optical sensor assembly including a light source or sources adapted to transmit light to the colorimetric indicator, and a photodiode or photodiodes configured to detect light reflected from the colorimetric indicator and to generate a measurement signal, and a processor in communication with the electro-optical sensor assembly. The processor can be configured to receive the measurement signal generated by the electro-optical sensor assembly and to compute a concentration of carbon dioxide based on the measurement signal. Methods for using the systems are also disclosed including providing a breathing therapy to a patient or user.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 14/902,075, filed Dec. 30, 2015, which is a 35 U.S.C. § 371 nationalphase application of International Application No. PCT/US2014/046803,filed Jul. 16, 2014, which claims the benefit under 35 U.S.C. § 119 ofU.S. Provisional Patent Application No. 61/846,742, filed Jul. 16, 2013,each of which is herein incorporated by reference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

FIELD

Embodiments described relate generally to quantitative colorimetriccapnometry methods and systems.

BACKGROUND

Methods and devices for measuring quantitative airway carbon dioxide(CO₂) gas exchange concentrations and respiratory rate of a subject'sbreath (capnometry) are well known in the clinical markets. In fact, theuse of capnometry during intubated surgical and otherwise criticalventilated patient situations is mandated by standards organizationsbecause it is critical in maintaining safety. By far the most commontechnology used in commercial instruments is IR spectroscopy because ofits accuracy, precision, speed of response and reliability. Infraredabsorption spectroscopy capnometers quantify the subject's airway CO₂gas exchange in real time without any airway perturbation or violationof sterility. Unfortunately, this utility requires substantialtechnological complexity and a high price when compared with othercommon medical parameter measurements such as temperature, bloodpressure, ECG, heart rate and pulse oximetry. Now that the use ofcapnometry has expanded outside the in-hospital environment topre-hospital emergency care including non-intubated subject monitoringapplications such as dentistry, pain management, conscious sedation,in-home use, etc., there is an increased awareness of the need for lessexpensive capnometry instruments.

There are many other techniques for measuring gas exchange in asubject's breath. Among these include mass spectrometry, Ramanscattering, photoacoustic, piezoelectric, paramagnetic and chemicalbased instruments. All of these techniques have specific tradeoffs withrespect to their complexity, performance and cost. In examining theaspects of these tradeoffs, one technique stands alone as havingpotential for simplicity, meeting adequate performance criteria atconsiderably lower cost than other methods; the chemical basedcolorimetric technique.

Chemical based colorimetric techniques have been utilized in many otherapplications including qualitative human breath CO₂ measurement.However, one of the challenges in using colorimetric techniques is itsability to achieve sufficient response time to capture rapidly changingCO₂ concentrations such as is found in a subject's ventilation pattern.Commercially available airway colorimetric products first appeared inthe late 1980's, but could only give relative qualitative indications ofCO₂ concentrations due to their slow response. In the 1990's,improvements to the indicator chemistry formulations were made toenhance the speed of response to breath-by-breath gas concentrationvariations. For example, in 1994 Dr. Andras Gedeon published testresults of a colorimetric indicator compared with an IR spectroscopybased capnometer showing significant similar breath-by-breath response.Details regarding these test results are described in the paper “A NewColorimetric Breath Indicator (Colibri)” published in Anaethesia (1994)volume 49, pages 798-803, which is herein incorporated by reference inits entirety. Since then, Dr. Gedeon and others have also developed andmanufactured qualitative colorimetric indicators primarily for use withintubation verification.

Although much has been done to improve chemical based colorimetrictechniques, there remains a need for a low cost quantitative CO₂ devicethat provides fast and accurate continuous measurement of a subject'sbreath-by-breath CO₂ levels. Moreover, there is a need for a portabledevice that can be used by patients at home or otherwise to monitor CO₂levels as part of a treatment protocol. As such, the embodimentsdescribed herein provide devices, systems, and methods for addressing atleast these concerns. For example, some embodiments provide forelectro-optical techniques instead of visual interpretation to detectthe color change from CO₂ concentrations. Other embodiments provide fordevices or systems that display continuous calibrated CO₂ concentrationsand respiratory rates using colorimetric indicator chemistry.Additionally, methods and devices contemplated herein include newtechniques for user calibration and unique patient attachments orpatient interface for various clinical applications to allowquantitative monitoring of a spontaneously breathing (non-intubated)subject with a completely robust, portable, very low cost, low powerinstrument. The simplicity of this instrument is suited, at least, forthe technology-unsophisticated, home-based user.

In addition, some embodiments described provide examples of breathingtherapy for treating any number of disorders including panic disorder,hypertension, post-traumatic stress disorder (PTSD), asthma etc.Although breathing therapies or methods (e.g. yoga and meditation) havebeen used in the past as ways to reduce anxiety or hyperventilation,such breathing techniques are focused primarily on relaxing or calmingthe practitioner and not on modifying carbon dioxide levels duringrespiration for treatment. In particular, previous techniques have notused a quantitative colorimetric carbon dioxide system for therapy. Assuch, the quantitative colorimetric devices and systems described hereincan be used to provide breathing therapy treatment by, for example,helping patients modify end-tidal CO₂ levels to help treat panicdisorder, PTSD, anxiety, general anxiety disorder, obsessive-compulsivedisorder, social phobia, depression, apnea, migraines, epilepsy, asthma,hypertension, conscious sedation, emergency medical services (EMS), etc.

SUMMARY OF THE DISCLOSURE

The present disclosure relates to quantitative colorimetric systems andmethods for using the same. The quantitative colorimetric systems can beused to provide a user with a breathing therapy.

In general, in some embodiments, quantitative colorimetric carbondioxide detection and measurement systems include: a gas conduit, acolorimetric indicator adapted to exhibit a color change in response toexposure to carbon dioxide gas, a temperature controller operativelycoupled to the colorimetric indicator and configured to control thetemperature of the colorimetric indicator, an electro-optical sensorassembly includes a light source or sources adapted to transmit light tothe colorimetric indicator, and a photodiode or photodiodes configuredto detect light reflected from the colorimetric indicator and togenerate a measurement signal, and a processor in communication with theelectro-optical sensor assembly. The processor is configured to receivethe measurement signal generated by the electro-optical sensor assembly.

This and other embodiments can include one or more of the followingfeatures. The processer can be further configured to compute aconcentration of carbon dioxide based on the measurement signal. Theprocessor can be within a housing of the quantitative colorimetriccarbon dioxide detection and measurement system. The system can furtherinclude a mobile display device, wherein the processor can be furtherconfigured to transmit the measurement signal to the mobile device andthe mobile device is configured to compute a concentration of the carbondioxide and a respiration rate based on the measurement signal. Thesystem can further include a display device, wherein the processor canbe configured to transmit the computed concentration of carbon dioxideto the display device and the display device is configured to displaythe computed concentration of carbon dioxide. The processor can beconfigured to control the temperature controller to maintain thecolorimetric indicator at a pre-determined temperature. Thepre-determined temperature can be from 20° C. to about 50° C. The systemcan further include a pump configured to move a sample of gas in the gasconduit into contact with the colorimetric indicator. The gas conduitcan include a separate disposable sample inlet tube containing thecolorimetric indicator. The disposable sample inlet tube can beconfigured to removably engage with and couple to the electro-opticalsensor assembly. The system can further include a display incommunication with the processor. The display can further be configuredto display a user interface for operating the system. The system canfurther include a sensor cable coupling the electro-optical sensorassembly to the processor. The system can be wearable. The system can beconfigured to continuously measure a user's exhaled air duringbreathing. The processor can be configured to provide a guided breathingmaneuver to thereby alter the amount of carbon dioxide measured from auser's exhaled air. The processor can be configured to provide visualand/or audio cues to guide the user's breathing. The processor can beconfigured to provide the user a guided breathing maneuver based on thequantity of carbon dioxide measured from the user's exhaled breath. Theprocessor can be configured to provide the user a guided breathingmaneuver based on the respiration rate measured from the user's exhaledbreath. The system can further include a nasal and/or oral cannulaadapted for collecting a sample of a user's exhaled breath for exhaledcarbon dioxide measurement. The cannula can be configured to be in fluidcommunication with the gas conduit. The gas conduit includes a nasaland/or oral cannula adapted for collecting a sample of a user's exhaledbreath for exhaled carbon dioxide measurement. The gas conduit caninclude the colorimetric indicator and nasal and/or oral cannula. Thegas conduit, colorimetric indicator, and nasal and/or oral cannula canbe configured for a single use. The processor can be configured tomeasure a respiration rate. The system can further include a deviceconfigured to electronically receive the computed CO₂ concentration andexecute a breathing therapy program that can further include a set oftone patterns adapted for guiding a user's breathing technique whilemonitoring the user's CO₂ levels. The tone patterns can correspond to atotal breath time, an inhalation time, an expiration time, a first pausetime between inhalation to exhalation, and a second pause time betweenexhalation and inhalation. The tone patterns can provide silence for thefirst and second pause times. The device can be configured to record theuser's information. The device can be configured to visually display agoal line corresponding to a target end-tidal CO₂ level on an end-tidalCO₂ graph. The device can be a mobile device. The electro-opticalassembly can include one photodiode and two alternating light sources.The electro-optical assembly can include two photodiodes and two lightsources. The pump can be upstream of the colorimetric indicator. Thepump can be downstream of the colorimetric indicator. The temperaturecontroller can be further configured to control a temperature of theelectro-optical sensor. The temperature controller can include a heater.The system can further include a temperature probe configured to measurethe temperature of the colorimetric indicator. The processor can beconfigured to apply a temperature correction to the measurement signalbased on the temperature of the colorimetric indicator.

In general, in some embodiments, breathing therapy methods include:

(1) receiving at least a portion of a user's exhaled air in a gas inletof a quantitative colorimetric detection system;

(2) measuring a user's end-tidal CO₂ levels with the quantitativecolorimetric detection system based on a color change resulting fromexposure of the system to the user's exhaled air; and

(3) outputting a set of visual and/or audio cues from the quantitativecolorimetric system with instructions for the user to adjust theirbreathing pattern to coincide with the cues to thereby modify the user'sexhaled CO₂ levels.

The breathing pattern can include the exhaled CO₂ level and respirationrate. The method can further include displaying the user's measured CO₂levels to provide visual feedback during treatment. The method canfurther include displaying the user's breathing rate to provide visualfeedback during treatment. The method can further include the therapydirecting the user's end-tidal CO₂ levels to a level between about 37mmHg and 43 mmHg. The outputting step can further include outputting aset of timed tones having an audible sequence of rising tones, fallingtones, and silence. The rising tones can indicate respiration, fallingtones can indicate expiration, and silence can indicate a pause in theuser's respiration. The adjusting step can further include the userbreathing in at the rising tones, breathing out at the falling tones andnot breathing during silent periods. The method can further includemeasuring a baseline CO₂ level for the user prior to modification. Themethod can further include treating post-traumatic stress disorder(PTSD), panic disorder, anxiety, asthma, hypertension,obsessive-compulsive disorder, social phobia, depression, apnea,migraines, or epilepsy by training the user to modify their exhaled CO₂levels. The method can further include controlling a temperature of acolorimetric indicator in the quantitative colorimetric detection systemwhile measuring the user's end-tidal CO₂ levels. The method can furtherinclude measuring a temperature of a colorimetric indicator in thequantitative colorimetric detection system while measuring the user'send-tidal CO₂ levels and applying a temperature correction to themeasured color change.

In general, in some embodiments, method for treating a user with a panicdisorder with a breathing therapy include:

(1) measuring a user's baseline end-tidal CO₂ and breathing rate. Theuser's CO₂ is measured with a quantitative colorimetric CO₂ detectionsystem;

(2) determining a target end-tidal CO₂ level and a target breathing ratefor the user; and

(3) outputting a set of tone patterns with instructions to modify theuser's end-tidal CO₂ levels and breathing rate from an audio deviceduring a first time period and discontinuing the output of the set oftone patterns during a second time period. The tone patterns areconfigured to guide the user's breathing pattern to achieve the targetend-tidal CO₂ level and target breathing rate.

In some embodiments the first time period can be about ten minutes orless. In some embodiments the second time period can be about fiveminutes or less. In some embodiments the set of tone patterns cancorrespond to a target breathing pattern. In some embodiments the targetbreathing rate can be between about six breaths-per-minute and 13breaths-per-minute.

In general, in some embodiments, quantitative colorimetric carbondioxide detection systems include: a colorimetric indicator adapted tochange color in response to exposure to a quantity of carbon dioxidegas, a temperature controller coupled to the colorimetric indicator andconfigured to control a temperature of the colorimetric indicator, anelectro-optical sensor assembly coupled to the colorimetric indicator, aphotodiode is configured to detect a first reflected light based on thefirst wavelength and a second reflected light based on the secondwavelength and to generate an first electrical signal based on the firstreflected light and a second electrical signal based on the secondreflected light, and a processor in communication with theelectro-optical sensor assembly and temperature controller. Theelectro-optical sensor assembly includes light sources adapted totransmit a first wavelength and a second wavelength to the colorimetricindicator. The first wavelength is configured to be sensitive to anindicator color change and the second wavelength is configured to not besensitive to an indicator color change. The processor is configured toreceive the electrical signals generated by the electro-optical sensorassembly. The processor utilizes the signals to compute the quantity ofcarbon dioxide exposed to the indicator.

The electro-optical sensor assembly can be configured to alternatelytransmit the first and second wavelengths.

In general, in some embodiments, methods of calibrating a quantitativecolorimetric carbon dioxide detection system include:

(1) exposing a chemical colorimetric indicator to a reference gas;

(2) transmitting light to a surface of the indicator while the indicatoris exposed to the reference gas;

(3) measuring a first color of the indicator based on the exposure tothe reference gas;

(4) exposing the indicator to an ambient gas;

(5) measuring a second color of the indicator based on the exposure tothe ambient gas;

(6) deriving a “span” calibration based on the difference between thefirst color of the indicator and the second color of the indicator; and

(7) applying the span calibration to a measurement of the color of theindicator exposed to a breath sample.

Exposing the chemical colorimetric indicator to a reference gas caninclude exposing the indicator to a sealed ampoule filled with areference sample having a known carbon dioxide concentration. Exposingthe indicator to an ambient gas can include removing the seal on theampoule to allow exposure of the indicator to ambient air.

In general, in one embodiment, a method for quantitatively measuringcarbon dioxide, includes:

(1) passing a sample gas through a gas conduit;

(2) contacting a colorimetric indicator with the sample gas. Thecolorimetric indicator is adapted to exhibit a color change in responseto exposure to carbon dioxide gas;

(3) controlling the temperature of the colorimetric indicator with atemperature controller coupled to the colorimetric indicator whilecontacting the colorimetric indicator with the sample gas;

(4) transmitting light to the colorimetric indicator with anelectro-optical sensor assembly comprising a light source or sourceswhile contacting the colorimetric indicator with the sample gas;

(5) detecting light reflected from the colorimetric indicator with aphotodiode;

(6) generating a measurement signal from the photodiode based on thereflected light;

(7) sending the measurement signal to a processor; and

(8) computing the concentration of carbon dioxide in the sample gas withthe processor based on the measurement signal.

Computing the concentration of carbon dioxide with the processor can bebased on the color change of the colorimetric indicator. The methods canfurther include maintaining the colorimetric indicator at apre-determined temperature with the temperature controller. Thepre-determined temperature can be from about 20° C. to about 50° C. Themethods can further include moving the sample gas in the gas conduitinto contact with the colorimetric indicator using a pump. The methodscan further include displaying a user interface for operating thesystem. The methods can further include continuously measuring a user'sexhaled air during breathing. The methods can further include providinga guided breathing maneuver to the user with instructions to alter theamount of carbon dioxide measured from the user's exhaled air. Themethods can further include providing visual and/or audio cues to guidethe user's breathing. The methods can further include measuring thebreathing rate of a user's breathing. The methods can further includeelectronically sending the computed CO₂ concentration to a device andexecuting a breathing therapy program comprising a set of tone patternsfor guiding a user's breathing pattern while monitoring the user's CO₂levels with the device. The device can be a mobile device with adisplay. The device can include a display. The breathing pattern caninclude the CO₂ levels and respiration rate. The tone patterns cancorrespond to a total breath time, an inhalation time, an expirationtime, a first pause time between inhalation to exhalation, and a secondpause time between exhalation and inhalation. The tone patterns canfurther provide silence for the first and second pause times. Themethods can further include recording the user's information with thedevice. The methods can further include visually displaying on thedevice a goal line corresponding to a target end-tidal CO₂ level on anend-tidal CO₂ graph.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe claims that follow. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 is a schematic diagram of a quantitative colorimetric carbondioxide detector system in accordance with some embodiments.

FIG. 2 is a schematic diagram of a quantitative colorimetric carbondioxide detector system in accordance with some embodiments.

FIGS. 3A-3B illustrate process flow charts in accordance with someembodiments.

FIG. 4 illustrates a quantitative colorimetric gas detector inaccordance with some embodiments.

FIG. 5 illustrates a quantitative colorimetric gas detector inaccordance with some embodiments.

FIGS. 6A-6D illustrate sample tube assemblies in accordance with someembodiments.

FIG. 7 shows an exemplary patient attachment mechanism with integratedgas sensors in accordance with some embodiments.

FIG. 8 shows a quantitative colorimetric gas component detector with anasal airflow sensing unit in accordance with some embodiments.

FIG. 9 shows a quantitative colorimetric gas component detector with anasal and oral airflow sensing unit in accordance with some embodiments.

FIG. 10 shows a headband for a quantitative colorimetric gas componentdetector system in accordance with some embodiments.

FIG. 11 shows a headband for a quantitative colorimetric gas componentdetector system with an attached sensing unit at the distal end of aflexible cable in accordance with some embodiments.

FIG. 12 shows a wearable quantitative colorimetric gas componentdetector system in accordance with some embodiments.

FIGS. 13A-13B shows a wearable a quantitative colorimetric gas componentdetector system according to some embodiments in accordance with someembodiments.

FIG. 14 illustrates an inspiration and expiration graph.

FIG. 15 illustrates a breathing therapy system according to embodimentsdescribed.

FIG. 16 illustrates a graphical representation of end-tidal CO₂ andbreathing rate in accordance with some embodiments.

FIG. 17 is a flowchart showing a three-stage treatment protocolaccording to embodiments described.

DETAILED DESCRIPTION

Quantitative colorimetric carbon dioxide detection and measurementsystems are disclosed herein. The systems can include a gas conduitconfigured to provide a carbon dioxide gas sample to a colorimetricindicator. The colorimetric indicator is adapted to exhibit a colorchange in response to exposure to carbon dioxide gas. An electro-opticalsensor assembly including a light source or sources can transmit lightto the colorimetric indicator. A photodiode or photodiodes can detectlight reflected from the colorimetric indicator and generate ameasurement signal corresponding to the color change of the colorimetricindicator in response to the exposure to carbon dioxide gas. A processorin communication with the electro-optical sensor assembly can receivethe measurement signal generated by the electro-optical sensor assemblyand compute a concentration of carbon dioxide based on the measurementsignal. Methods for using the systems are also disclosed includingproviding a breathing therapy to a patient or user.

Reference will now be made in detail to exemplary embodiments of theinvention, examples of which are illustrated in the accompanyingdrawings. While the invention will be described in conjunction with theexemplary embodiments, it will be understood that they are not intendedto limit the invention to those embodiments. On the contrary, theinvention is intended to cover alternatives, modifications andequivalents, which may be included within the spirit and scope of theinvention as defined by the appended claims.

Various embodiments disclosed herein are directed to devices and systemsthat provide quantitative colorimetric CO₂ measurement from a breathsample. FIG. 1 shows an example of a quantitative colorimetric CO₂detection system. The detection system 100 may include an inlet/conduit102 directing a breath sample or a gas to enter the detection system. Insome embodiments, the inlet/conduit 102 may be coupled to or can includea gas or fluid conduit to allow gas to pass from the inlet/conduit 102to a colorimetric indicator 104. In some embodiments, the inlet/conduit102 may connect to or be in fluid communication with a sensing chamberhaving sensing elements, such as a colorimetric indicator andelectro-optical assembly.

Once a gas sample, which may be a portion of a patient's exhaled breathor the complete exhaled breath, reaches the colorimetric indicator 104,the colorimetric indicator 104 changes color based on the volume percentconcentration of CO₂ exposed to the indicator 104. For example, in someembodiments, the colorimetric indicator 104 is blue when less than 0.5%CO₂ is present, blue-green when 1% to 2% CO₂ is present, green when 2%to 3% CO₂ is present and yellow when approximately 5% CO₂ is present.The specific colors visually apparent at specific CO₂ concentrationslevels within the range of approximately 0.5% to 5% can be adjusted withdifferent chemistry formulations.

With quantitative CO₂ colorimetric measurements, once the color shift isdetermined, it can be desirable that the specific color shift atspecific CO₂ concentrations is repeatable. This may involvemanufacturing quality assurance processes to validate thischaracteristic within various batches of colorimetric material.

In some embodiments, the concentration of carbon dioxide detected by theindicator is used to determine or derive a partial pressure for thecarbon dioxide in the gas or breath sample. For example, if a totalpressure of a breath sample is known (or measured) and the percentage ofcarbon dioxide present in that breath sample is measured, then thepartial pressure of the carbon dioxide in the sample can be calculatedor derived. Additionally, in some cases, calculations are performed todetermine a mean, median, or mode gas component value. In some cases,the carbon dioxide values measured in multiple breaths (e.g. more thanone exhalation or inhalation) are averaged to determine a computedaverage carbon dioxide value.

In further embodiments, the indicator is adapted to change color basedon the partial pressure of carbon dioxide present. In some cases, theindicator is adapted to change color according to partial pressures ofabout 7.6 mmHg (first color); 15.2 mmHg (second color); 22.8 mmHg (thirdcolor); 30.4 mmHg (fourth color); and 38 mmHg (fifth color) of a gascomponent such as carbon dioxide.

Several different chemical formulations for colorimetric indicators canbe used in the contemplated embodiments. Some embodiments include achemical colorimetric indicator having a substrate with a reagent thatis reactive to CO₂. Once the substrate is exposed to the CO₂, thereagent reacts to create a color change in the substrate. In someembodiments, the indicator is a thin film or membrane with a CO₂sensitive reagent. In some embodiments, for quantitative measurements,the color shift in the presence of CO₂ is indicated on both sides of thefilm.

Referring again to FIG. 1 , the colorimetric indicator may be coupled toan electro-optical sensor assembly 106. The electro-optical sensorassembly may be configured to detect the color change in thecolorimetric indicator. For example, the assembly 106 may include alight source/emitter such as a mono, bi or tri-color LED assembly thatis combined and pulsed to emit certain wavelengths of light ranging fromnear infrared to ultraviolet that in turn are transmitted to a surfaceof the colorimetric indicator. Some of the light that encounters thesurface of the indicator will be reflected, scattered, or absorbed bythe indicator. Light reflected back from the indicator may besynchronously detected by a photodetector such as one or morephotodiodes that generates an electrical signal based on the detectedreflected light.

In some embodiments, an indicator color change is detected bydetermining the intensity and wavelength shift in the light reflectedfrom the indicator. In some cases, a reference light source having oneor more reference wavelengths is alternately transmitted to theindicator surface. For example, a light of a first wavelength may bealternated with a light of a second wavelength for transmission to theindicator. The reference wavelength(s) may be selected so as to not besensitive to the CO₂ induced wavelength shift but are sensitive to otherfactors such as surface contamination, ambient light, opticsmisalignment, temperature effects and colorimetric indicator aging. Amicroprocessor can be employed to compare the reference reflected lightoutput with the reflected light output from the CO₂ induced signal tocompensate for artifact and provide other user error messages. In somecases, the reference wavelength that is not sensitive to the indicatorcolor shift is used to determine measuring conditions (includingcompensation factors).

Additionally, calibration methods may incorporate a ratiometric, dualwavelength electro-optical measurement system which rejects common modeinterferences such as: misalignment of indicator/sensor combination,electro-optical component drift, ambient temperature effects, ambientlight effects, indicator contamination (mucus, moisture, dust, airpollution compounds), presence of anesthetic agents or nebulizedmedications, indicator aging phenomena; batch to batch chemistryvariability, etc. Ratiometric measurements that may be suitable includethose commonly used with other optically based sensor systems such as IRspectroscopy based capnometers and pulse oximeters.

As described, the electro-optical assembly 106, shown in FIG. 1 , mayinclude one or more light emitter(s), one or more photodetector(s), andother suitable components such as a lens, diffuser or collimator. Insome embodiments, the photodetector receives the reflected light fromthe indicator and generates an electrical signal. The electrical signalmay be transmitted to a microcontroller or a processor. Depending on thereflected light received by the photodetector, the photodetector maygenerate one or more electrical signals based on the received reflectedlight. For example, if a first electric signal may be generated for afirst detected reflected light and a second electric signal may begenerated for a second detected reflected light. The first and secondsignals may be used for comparison or computation to measure the testedgas component in the sample. In some embodiments one or morephotodetectors can be used with the one or more light emitters. Forexample, two light emitters could be used with two correspondingphotodetectors.

The operating electronics 108 may include a processor configured toreceive the electrical signal(s) from the photodetector(s). Theprocessor may be further configured to process the electrical signal andcompute the amount of CO₂ in the gas sample. The amount of CO₂ may becomputed in any suitable units including concentration percentage in thebreath sample or CO₂ partial pressure (mmHg). In some variations, thepressure of the CO₂ can be derived from other measured values such asconcentration percentage. In Some embodiments the processor is withinthe housing of the device. In some embodiments the processor is incommunication with the system and receives the electrical signal. Insome embodiments the processor is external to the quantitative detector.

Additionally, in some embodiments, the processor includes calibrationdata for the system, which is used to determine the quantity of CO₂based on the color shift detected by the electro-optical assembly 106.In some embodiments a calibration can be applied to the color shiftdetected by the electro-optical assembly based on a temperature of thecolorimetric film or breath sample. The temperature correction orcalibration can be a look-up table or formula tailored to the specificcolorimetric material. In some embodiments the temperature correction orcalibration is applied to the measurement signal by the processor.

In further embodiments, the detection system 100 may include a displayor monitor 110. The display 110 may include a user interface for userinformation input. In other variations, the display 110 may display thecomputed CO₂ measurements. The CO₂ measurement values may be in anysuitable units including pressure units of Torr or mmHg. In furtherembodiments, the display 110 may output visual or audio cues guiding theuser through a breathing maneuver to modify CO₂ levels. In otherembodiments the display 110 may be wirelessly connected to the internetincluding cloud based computational methods. In some embodiments, thedisplay is not a separate component and is instead integrated with theoperating electronics 110. For example, the operating electronics anddisplay may be a mobile device such as a smart phone, tablet, or othercomputing device programmed to interface with and operate one or more ofthe electro-optical sensor assembly, colorimetric indicator, and inlet.In some embodiments the display is a non-mobile device. For example, thedisplay could be a television or monitor that receives the image data todisplay. In some embodiments the processor could be attached to or incommunication with the television, for example as a gaming system, mediastreaming device, antenna, or other device configured to provide imagedata to an input on a display.

FIG. 2 shows additional details regarding another embodiment of aquantitative colorimetric CO₂ detection system 103. The system 103includes a gas permeable shield or protective shield 114 around acolorimetric chemical indicator 116. In some cases, the shield protectsthe indicator from physical contamination, such as touching by a user,while allowing fluid (e.g. gas) movement through the shield to theindicator. In some embodiments, an annular ring surrounds and shieldsthe indicator from unwanted contaminating contact. For example, theannular ring may include a cavity in which the indicator sits. The ringmay be porous or otherwise gas permeable to allow gas movement to theindicator through the ring.

In some variations, the colorimetric indicator is a thin film ormembrane having a reagent that is reactive to CO₂. Upon exposure to CO₂,the reagent reacts to create a color change. In other embodiments, thecolor change is indicated on both sides of the thin film or membrane.Advantageously, in some variations, the color change is optically orvisually detectable. In some cases, the colorimetric indicator/sensorcan be made very small/lightweight (<0.125″ diameter) and thus can beplaced directly in the exhaled breath flow path. In some embodiments,there is no gas entrainment (vacuum pump) required. As such,colorimetric CO₂ sensing can combine the advantages of both sidestreamcapnometers (easily attached to non-intubated subject) and mainstreamcapnometers (no time delay, no pump, no sample line plugging). Theentire sensor assembly could also be disinfected.

As shown in FIG. 2 , the colorimetric indicator 116 can be positioned ona transparent window 118. In some embodiments, the indicator 116 isaffixed or adhered to the window 118. The transparent window 118 allowsthe transmission of light to a surface of the indicator. Thetransparency also allows reflectance of the light from the indicator toan electro-optical assembly 120 coupled to the colorimetric indicator.In other embodiments, the window 118 may be a plate or substrate that issubstantially optically clear such that visible light can transmit (andreflect) therethrough.

In some embodiments, the colorimetric chemistry indicator is containedwithin a clear sealed plastic gas filled cell while allowing the sensorto record the color. After this “span” calibration to a known gasconcentration is recorded in the processor, the operator is thenprompted to peel off the plastic gas filled cell exposing the indicatorto the environment (e.g. ambient air) and at that time the processorwill perform a “zero” calibration point before attaching theindicator/sensor to the subject. Alternate calibration techniques mayemploy inserting a known color sample unaffected by the presence of CO₂while still reflecting light back to the sensor. As described, in otherembodiments, calibration methods may incorporate a ratiometric, dualwavelength electro-optical measurement system which rejects common modeinterferences.

The electro-optical assembly 120 may include one or more pulsed lightemitters or sources such as an LED. Each light emitter transmits a knownwavelength of light to a surface of the indicator 116 through thetransparent window. Varying amounts of light will reflect from theindicator 116, which is undergoing color shift from exposure to CO₂,back toward the electro-optical assembly 120. A photodetector such as aphotodiode detects the amount of reflected light resulting from thecolor shift and generates a CO₂ concentration signal that is transmittedto an electronics module 124. In some cases, a cable 122 couples theelectro-optical assembly 118 to the electronics module 124.

The electronics module 124 may include a power supply (e.g. battery) forthe system 103. Advantageously, embodiments contemplated will requirelow power for operation. Many hours of operation are contemplated withthe use of hearing aid batteries. In other embodiments rechargeableLithium ion batteries may be employed as a power source.

In other variations, the electronics module 124 has a microcontroller orprocessor configured to operate the system. In further variations, theprocessor/microcontroller receives the signal(s) generated by theelectro-optical assembly and computes a CO₂ measurement for the gassample based on the signal. As part of the CO₂ computation, theprocessor/microcontroller may include calibration data and the methodsfor the system described herein. The processor can calculate additionalcharacteristics of the gas sample, such as the respiration rate of theuser or patient. The calibration data may include a calibration curvespecific to the particular colorimetric chemical formulation. Thecalibration data can also include temperature correction data for theparticular colorimetric chemical formulation. The calibration data maybe stored in flash memory or in the processor.

In further variations, the system 103 may include an indicator housingthat holds the protective shield 114, indicator 116, and transparentwindow 118. The indicator housing may be disposable, replaceable, orotherwise removable from the system 103. The separate sensor housing mayalso contain the electro-optical assembly and, optionally, the sensorcable. The sensor housing may be releasably coupled to the indicatorhousing holding the shield, indicator, and transparent window. Thisallows removal and replacement of the indicator once indicator use hasbeen exhausted. For example, a chemical colorimetric indicator may last24 hours of use and require replacement for continued operation of thedetection system.

In further embodiments, an indicator unit that includes the indicator, aprotective shield, and an optically transparent substrate may beintegrated with a user interface to detect a breath sample from the noseor mouth. For example, the indicator unit may be formed as a nasal ororal interface that is easily attached near, on, or adjacent to anairway or airflow. The indicator unit may be clipped, for example, tothe nose to monitor and measure a patient's CO₂ levels. In someembodiments, a disposable indicator unit can be attached and detachedfrom a reusable electro-optical sensor assembly. This could include atiny magnetic latching mechanism or any other suitable attachment means.Other means of attachment/detachment could employ a plastic molded snapon-off mechanism or a quarter-turn latch mechanism.

FIG. 2 shows a display module 126 may be either hardwired or wirelesslyconnected to the electronics module 124. The display module may includea computer such as a mobile device or a handheld device that is capableof displaying instructions, CO₂ measurements, or a breathing protocol.In further embodiments, the electronics module 124 and display module126 are a single unit or device. The entire system 103 may be portableand/or handheld.

FIGS. 3A and 3B illustrate embodiments of flow charts 200, 250 forprocess flows. As shown in FIGS. 3A-3B a carbon dioxide sample 201, 251enters a gas or fluid conduit 202, 252 and contacts the colorimetricindicator 204, 256. A pump 206, 254 can be used to pump the carbondioxide into contact with the colorimetric indicator. The pump can bedownstream of the colorimetric indicator (FIG. 3A) or upstream of thecolorimetric indicator (FIG. 3B). The carbon dioxide can exit 208, 258the system after contacting the colorimetric indicator 204, 256. Theelectro-optical sensor assembly 210, 260 interrogates the colorimetricindicator 204, 256 when the carbon dioxide stream contracts thecolorimetric indicator 204, 256. The electro-optical sensor assembly210, 260 outputs a measurement signal 212, 262 based on theinterrogation of the colorimetric indicator 204, 256. The measurementsignal 212, 262 can be sent to an onboard processor 214, 264 thatanalyzes the measurement signal 212, 262 to determine the amount ofcarbon dioxide contacting the colorimetric indicator 204, 256. As analternative option the measurement signal 212, 262 can be transmitted toan external processor 220, 270 with the external processor determiningthe amount of carbon dioxide that contacts the colorimetric indicator204, 256. Data associated with the interrogation of the colorimetricindicator can then be displayed 216, 222, 266, 272. The display can beonboard the device (216, 266), external to the device (222, 272), partof a tablet, smartphone, or computer in communication with the device.

FIG. 4 illustrates an example of a patient using a quantitativecolorimetric carbon dioxide measuring system 300 in some embodiments.Exhaled breath of the patient enters an inlet 302, illustrated as anasal cannula, and flows through a conduit or cannula 304 and into thequantitative colorimetric carbon dioxide measuring system 300.

FIG. 5 illustrates a schematic of a quantitative colorimetric carbondioxide measuring system 300 in accordance with some embodiments. Thesystem 300 includes a conduit or inlet 303. The conduit or inlet 303 canbe configured to receive or engage with a cannula, sample inlet tube, orother conduit such that the cannula, conduit, or inlet is configured tointroduce a gas sample to the system 300. FIGS. 6A-6D illustrate variousconfigurations of sample tube assemblies that can be connected to thesystem 300 via conduit or inlet 303. In some embodiments the gas conduitincludes or is configured to removably engage with a separate disposablesample inlet tube. In some embodiments the gas conduit includes or isconfigured to removably engage with a nasal and/or oral cannula adaptedfor collecting a sample of a user's exhaled breath for exhaled carbondioxide measurement with the nasal and/or oral cannula configured to bein fluid communication with the gas conduit.

The system 300 can include a colorimetric indicator 305 within a housing301 of the system 300. An electro-optical sensor 306 can be included tointerrogate the colorimetric indicator 305.

A temperature controller 308 can be provided to control the temperatureof the colorimetric indicator and/or the temperature of the incoming gassample. The temperature controller can control a heater and a cooler tocontrol the temperature of the colorimetric indicator and/or incominggas sample to a pre-determined temperature. In some embodiments thepre-determined temperature is from about 20° C. to about 50° C. In someembodiments the processor can be configured to control the temperaturecontroller. In some embodiments the temperature controller can also beconfigured to control a temperature of the electro-optical sensor. Insome embodiments a temperature probe can be used to measure thetemperature of the colorimetric indicator, incoming gas sample, and/orelectro-optical sensor.

A pump 310 can be included within the housing 301 to pump the incominggas sample. In some embodiments the pump 310 can be located downstreamof the colorimetric indicator to effectively pull the incoming gassample passed the porous colorimetric indicator. In some embodiments thepump can be upstream of the colorimetric indicator to pump the gassample passed the colorimetric indicator. In embodiments including aheater as part of the temperature controller, the pump can improve heattransfer between the colorimetric indicator and heater by increasingcontact between the colorimetric indicator and heater.

The system 300 includes operating electronics 312. The operatingelectronics can control the system to perform various processing stepsas described herein. In some embodiments the operating electronicsreceive the measurement signal from the electro-optical assembly andcalculate properties associated with the measurement signal. In someembodiments the operating electronics receive the measurement signal andsend the measurement signal to a processor external to the system 300,with the external processor performing the calculations and analysis ofthe measurement signal. In some embodiments the system 300 includes awireless transmitter 314 to transmit data to an external processor, suchas a processor on a computer, tablet, or smartphone.

The system 300 can include a power supply 318 to power the components ofthe system 300.

In some embodiments the system 300 can include a display 316 with thehousing 301. In some embodiments the display is external to the system.For example, the display data can be wirelessly transmitted to a devicehaving a display, such as a computer, smartphone, tablet, flat screenmonitor, television, etc. In some embodiments a tablet or smartphone 320can be used with the system 300. The tablet 320 can include a processor322 and display 324. In some embodiments the processor 322 can receivethe measurement signal transmitted by the system 300 and analyze themeasurement signal to determine properties associated with themeasurement signal. In some embodiments the processor 322 is configuredto receive data from the system 300 and display the data on the tablet320 display 324. Decreasing the processing steps performed by theprocessor on board the system 300 can reduce the complexity and cost ofthe system 300.

FIGS. 6A-6D illustrate configurations of sample tube assemblies inaccordance with some embodiments. The sample tube assemblies illustratedin FIGS. 6A-6D can be used with the systems 300 illustrated in FIGS. 4and 5 . For example, the sample tube assemblies illustrated in FIGS.6A-6D can be configured to plug in to or snap into engagement with thesystem 300. The sample tube assemblies illustrated in FIGS. 6A-6D can bedisposable/configured for a single use.

FIG. 6A illustrates a sample tube assembly 400 having an inlet 402 andtube, conduit, or cannula 404. The sample tube assembly 400 can beengaged with a replaceable colorimetric material or cartridge 406. Thecolorimetric material 406 can removably engage with the tube, conduit,or cannula 404. An end 408 of the sample tube assembly can snap into theinlet 303 of the system 300 such that the colorimetric material 406 canbe interrogated by the electro-optical sensor 306. In some embodimentsthe sample tube assembly 400 is designed for a single use. In someembodiments the sample tube assembly 400 can be used multiple times withthe colorimetric material 406 periodically replaced. When the sampletube assembly 400 is used with embodiments of the system 300, thecolorimetric material would be provided by the sample tube assembly 400and would not be included within the housing 301 of system 300.

FIG. 6B illustrates a sample tube assembly 420 with an inlet 422,tube/conduit/cannula 424, and a built in colorimetric material 426 atend 428. The sample tube assembly 420 end 428 can engage with the inlet303 of the system 300 such that the colorimetric material 426 can beinterrogated by the electro-optical sensor 306. The sample tube assembly420 can be designed for single use such that the sample tube assembly420 can be used until the colorimetric material 426 expires. When thesample tube assembly 420 is used with embodiments of the system 300, thecolorimetric material would be provided by the sample tube assembly 400and would not be included within the housing 301 of system 300.

FIG. 6C illustrates a sample tube assembly 440 with an inlet 442,tube/conduit/cannula 444, and built in colorimetric material 446 withgas chamber 448 at end 450. The sample tube assembly 440 can engage withthe inlet 303 of the system 300 such that the colorimetric material 446can be interrogated by the electro-optical sensor 306. The sample tubeassembly 440 can be designed for single use such that the sample tubeassembly 440 can be used until the colorimetric material 446 expires.When the sample tube assembly 440 is used with embodiments of the system300, the colorimetric material would be provided by the sample tubeassembly 400 and would not be included within the housing 301 of system300.

FIG. 6D illustrates a sample tube assembly 460 with an inlet 462,tube/conduit/cannula 464, colorimetric material 466, and electro-opticalsensor 468 at end 470. The sample tube assembly 460 can engage with theinlet 303 of the system 300 such that the colorimetric material 466 andelectro-optical sensor 468 can communicate with the system 300. Thesample tube assembly 460 can be designed for single use such that thesample tube assembly 460 can be used until the colorimetric material 466expires. When the sample tube assembly 460 is used with embodiments ofthe system 300, the colorimetric material and electro-optical sensorwould be provided by the sample tube assembly 400 and would not beincluded within the housing 301 of system 300.

The inlets 402, 422, 442, and 462 of sample tube assemblies 400, 420,440, and 460 can be connected to the user or patient by any of thestructures illustrated herein or by conventional techniques. The inlets402, 422, 442, and 462 can also be coupled to accessories configured toattach to the user's nose or mouth. For example, the inlets 402, 422,442, and 462 can be configured to removably engage with and couple to anasal and/or oral cannula adapted for collecting a sample of a user'sexhaled breath for exhaled carbon dioxide measurement. In someembodiments the inlets 402, 422, 442, and 462 can be configured for usewith intubated patients.

The quantitative colorimetric carbon dioxide measuring system mayinclude computer software instructions or groups of instructions thatcause a computer or processor to perform an action(s) and/or to makedecisions. In some variations, the system may perform functions oractions such as by functionally equivalent circuits including an analogcircuit, a digital signal processor circuit, an application specificintegrated circuit (ASIC), or other logic device. In some embodiments,the image recording system includes a processor or controller thatperforms the functions or actions as described. The processor,controller, or computer may execute software or instructions for thispurpose.

“Software”, as used herein, also known as firmware includes but is notlimited to one or more computer readable and/or executable instructionsthat cause a computer or other electronic device to perform functions,actions, and/or behave in a desired manner. The instructions may beembodied in various forms such as objects, routines, algorithms, modulesor programs including separate applications or code from dynamicallylinked libraries. Software may also be implemented in various forms suchas a stand-alone program, a function call, a servlet, an applet,instructions stored in a memory, part of an operating system or othertype of executable instructions. It will be appreciated by one ofordinary skill in the art that the form of software may be dependent on,for example, requirements of a desired application, the environment itruns on, and/or the desires of a designer/programmer or the like. Itwill also be appreciated that computer-readable and/or executableinstructions can be located in one logic and/or distributed between twoor more communicating, co-operating, and/or parallel processing logicsand thus can be loaded and/or executed in serial, parallel, massivelyparallel and other manners.

Patient Interface

There are many different methods of attaching the colorimetric CO₂sensor to the patient or otherwise interfacing with the patient. Thosemethods may be different for different applications in the home,pre-hospital or clinical. Some of these methods are, but not limited to:over the ears similar to a nasal sampling cannula, a boom-like structuresimilar to a wireless headset with sensor placement near the nares; anasal alar clip; elastic band with cup collection chamber for sensingoral/nasal exhaled air; an inline airway adapter for use with intubatedpatients; a non-toxic (peel and stick) adhesive sensor assemblyattachment to the nares or upper lip with an ear clip cable strainrelief; incorporate sensor and electronics into a pair of eyeglasseswith an optional heads up display of CO₂ concentration and respirationrate; a headband containing the sensor/cable, electronics and powersupply wirelessly connected to the remote display. Any of theseattachment structures can be used with the devices disclosed herein. Insome embodiments the devices described herein can be designed for usewith intubated patients.

FIG. 4 illustrates an example of a patient using a sidestream embodimentof a quantitative colorimetric carbon dioxide measuring system 300 witha sample tube that is in an over-the-ear attachment mechanism. Exhaledbreath of the patient enters an inlet 302, illustrated as a nasalcannula, and flows through a conduit or cannula 304 and into thequantitative colorimetric carbon dioxide measuring system 300. The inlet302 can be clipped to the nose, e.g. the nasal alar cartilage.

FIG. 7 shows an exemplary embodiment of a quantitative colorimetric CO₂detection system with a patient attachment mechanism. In someembodiments, the sensing unit 704 contains the colorimetric indicatorand the electro-optical sensor assembly. In further variations, thesensing unit 704 may include a protective shield and optically clearindicator substrate as described above. The sensing unit 704 may beattachable to the patient by way of clips that attach to the nose, e.g.nasal alar cartilage.

In further embodiments, a small flexible insulated wire cable 702 leadsfrom the sensing unit 704 back to an electronic module, which is locatedon a headband or a headphone embodiment. The colorimetric CO₂ sensorcould be combined with a pulse oximeter sensor on the same nasal alarsite, expanding use to other monitoring applications.

In further variations, an adjustable (malleable) rod or boom-likestructure may be used to adjustably position the sensing unit 704 in thepatient's nasal airflow. In some cases, a connecting cable may runthrough the malleable rod to connect the sensing unit to an electronicmodule.

As shown in FIG. 7 , in some cases, the patient relaxes and breathesthrough her/his nose to provide a breath sample for CO₂ measurement.

FIG. 8 shows another example of a patient attachment mechanism where thesensing unit 804 is attached to straps or cables 802 that connect to ahandheld electronics module 808 that can optionally include a display.

Referring to FIG. 9 , a wearable quantitative colorimetric CO₂ detectorsystem having a patient attachment mechanism is shown. The system 900shown is capable of sampling both nasal and oral breathing patterns. Thesystem 900 may be configured to alternate between sampling nasal or oralbreath. Alternatively, the system may also sample only nasal or oralbreath per measurement. As shown, the CO₂ colorimetric sensing unit 904may include one or more inlets to both the nasal and oral airways. Thesensing unit 904 may optionally operate a single inlet to allow eithernasal or oral air to enter the sensing unit. In other variations, thesensing unit may include more than one inlet for capturing an air samplefrom either the nasal or oral airflow. In some variations, two or moreseparate indicator/sensor assemblies may be used to test air from eachor either nasal and/or oral source. Cable 902 is coupled to the sensingunit 904 and is in electrical communication with an electronics module.In some cases, the electronics module is located remote from thepatient. In other variations, the electronics module is integrated intoa wearable article such as a headband.

In a further embodiment, the sensing unit 904 may include the indicatorand the electro-optical sensor assembly. Alternatively, the sensing unit904 may include the indicator and a light guide such as an optical fibermay optically couple the indicator to a remotely located electro-opticalsensor assembly. For example, the colorimetric indicator chemistry maybe affixed at the end of a plastic optical fiber with the electro-opticscomponents at the other end. This could be useful in MRI imagingapplications.

Various embodiments of wearable electronics modules would permitprivate, unrestricted, unobtrusive mobility and portability. Moreimportantly, a wearable device would also allow the subject's hands tobe unencumbered allowing other functions (eating, washing hands, holdingreading material, writing, phone calling, etc.) The battery operatedsystem could be used while the subject is ambulatory, sleeping and/ordoing daily activities without being tethered to a restrictive samplingline, a bulky electronics/display module or power cord. These variousembodiments would include but not limited to the electronics module:affixed or integrated into a headband, placed on back side of ear (likea hearing aid), contained within an audio headset or enclosed withlanyard worn around the neck. In all these wearable embodiments, theelectronic module may employ Bluetooth wireless connectivity to remotedisplay/storage devices (custom unit, smartphone, tablet, laptop, etc.)

FIG. 10 shows a headband 1000 with a headband portion 1002 and ends1004. The headband depicted incorporates the electronics module withinthe headband portion and/or ends 1004. The headband 1000 includes aconnection port for coupling to a sensing unit as described above. Aflexible sensor cable (not shown) may be used to couple the sensing unitto the headband electronics module. The sensing unit may be attachableto an airflow airway structure such as the nasal alar as suggestedabove.

FIG. 11 shows an alternate headband 1100 configuration depicting asimilar cable attachment 1103 and a sensing unit 1104. The electronicsmodule may be contained in the headband such as at the lateral caps1108. In some embodiments, the wearable units described can connectthrough wired or wireless means to a processor or a display (e.g. smartphone) for operation of the detection systems. Instead of an earattachment, the sensor could be clipped to the nasal alar.

FIG. 12 shows another wearable colorimetric carbon dioxide detectiondevice 1200. The device 1200 includes two ear pieces 1208 and amalleable rod or boom-like structure 1202 with a sensing unit 1204 atthe distal end. The addition of a microphone may be employed to allowthe user to record audible messages. The device 1200 may include a cableleading from the head worn attachment to a belt-worn remote electronicsmodule.

FIGS. 13A-13B depicts a headphone embodiment. As shown, the electronicsmodule and battery would be incorporated into the headphones. Theheadphones 1300 would enable private audible commands, alerts, breathinginstructions, (calming music), etc. thus eliminating the need for thesubject to visually watch a remote digital display module. In certainapplications and clinical situations, this embodiment may even eliminatethe requirement for the separate remote visual display module. With theheadphones securely in place, an adjustable (malleable) connecting rod1302, incorporating the sensor wiring, the colorimetric sensor 1304 andan optional microphone is positioned near the subject's nose and mouth.

In some embodiments the colorimetric film can be part of a disposableportion of the device. For example, the colorimetric indicator film canbe included with or integral with a disposable inlet or sample tubeassembly. FIGS. 6A-6D illustrate embodiments of disposable sample tubeassemblies. The colorimetric indicator film can be provided as aremovable and disposable module that engages with the inlet tubeassembly. The colorimetric indicator film can be provided with theelectro-optical module. The colorimetric indicator film can be removablerelative to the electro-optical module. The colorimetric indicator filmcan be provided with or as part of an assembly including a protectiveshield designed to reduce ambient light.

For intubated spontaneous breathing patients the device can be similarto the sidestream embodiments disclosed herein. For example, the inletcould include a disposable assembly containing the colorimetricindicator film as illustrated in FIGS. 6A-6D. The disposable assemblycan allow the operator or patient to easily and conveniently attach andremove the assembly from an electro-optical sensor assembly at somepredetermined cycle to ensure system performance. The disposableassembly containing the colorimetric film can be replaced when needed.

Locating the electro-optical assembly further away from the patient'smouth can have a number of design advantages. Locating theelectro-optical assembly further away from the patient's mouth/nose canmake it easier to isolate the sensor from environmental effects liketemperature variation and ambient light. A larger and cheaperelectro-optical assembly can also be used when it is not located inclose proximity to the user's mouth. In addition, locating the sensorassembly further away from the patient's mouth reduces damage and wearand tear on the electro-optical assembly. Locating the electro-opticalassembly away from the patient's nose and mouth also allows for a lessbulky and intrusive sample collection adjacent to the patient's nose andmouth.

A sample tube can be used to receive a portion of the gas stream samplefrom the subject's breath and conducting it via a small, disposable,inexpensive cannula to the electro-optical sensor. The sample tube canbe connected to a remote enclosure containing the gas sensor andprocessing electronics. The sample tube can be connected to any of theembodiments of sample tube assemblies illustrated in FIGS. 6A-6D. Inmost cases the sampling line is a small diameter plastic assembly. Thesampling line can be affixed to the patient in an “over-the-ears”fashion depicted in FIGS. 7-9, 12, and 13A-13B. Over-the-ears subjectattachment can be used for clinical monitoring of both sedated andconscious subjects. For those few subjects who dislike or object towearing the over-the-ears cannula, alternate patient attachments canalso be used. Additionally, an exhaled gas collection cup could beemployed near the end of the sample line to enhance sampling of exhaledgas simultaneously from both the subject's nose and mouth.

In another example, the colorimetric sensor can be located in closeproximity to the patient's nose or mouth to receive the exhaled gas witha fiber optic cable connecting the colorimetric sensor color to theremote electro-optical assembly.

The advantages of enclosing the colorimetric indicator sensor andassociated electronics inside a remote enclosure are multifold with thesampling tube embodiments. First and foremost, a “light tight” remoteenclosure can prevent ambient light from interfering with the sensor.The remote enclosure can facilitate isolating the colorimetric indicatorfrom reflected visible light interference. In addition, the somewhatfragile electro-optical components and colorimetric film can be locatedfurther away from the user's mouth, making the electro-optical sensorless likely to be subject to spills, loss, or other forms of damage oruser abuse.

The sidestream configurations the colorimetric indicator can also beless susceptible to temperature variations in the ambient environmentand the patient's expired air. The exhaled breath sample is aspiratedthrough the sampling cannula, such as the sample tube assembliesillustrated in FIGS. 6A-6D, such that the temperature of the exhaledbreath sample equilibrates to the ambient air temperature beforecontacting the colorimetric sensor indicator thereby reducingtemperature variation effects. In some embodiments a thermal sensor orprobe can be placed inside the sensor chamber to provide furthertemperature compensation. In another alternative a temperaturecontroller, such as a micropower temperature controller, can be used tohold the colorimetric indicator at a constant temperature to improvesystem accuracy and precision as well as prevent moisture fromcollecting on the indicator surface. For the sidestream embodiments apump can be used to pump the breath sample. The pump can be downstreamof the colorimetric indicator or upstream of the colorimetric indicatorand can improve contact between the colorimetric indicator and thetemperature controller.

Additional advantages of embodiments contemplated and described hereininclude: (a) very low cost-complexity similar to typical portable pulseoximeter sensors and electronic readout; (b) very low powerconsumption-extremely portable with hearing aid style battery power; (c)simple to self-attach, unobtrusive and comfortable to wear; (d) easyuser calibration (simple mechanical action while connecting disposableindicator to sensor); (e) indicator/sensor combo is non-toxic, humidityinsensitive, very small, lightweight, waterproof and potentiallysterilizable; (f) no sensitivity to anesthetic agents, nebulizedmedications, visible light, magnetic fields, RF, air particulates,acoustic noise, shock and vibration; (g) no instrument warm up time isrequired-simple push on button, auto power off, power on/breath detectindicator LED, error messages; (h) no aspirating pump required thus notransit time readout delay and no “sampling line” plugging; (i)home-based biofeedback CO₂ concentration monitoringapplications—including Panic Disorder, PTSD and Asthma; (j) monitoringcapability in pre-hospital emergency medical services, conscioussedation, sleep monitoring, dentistry, veterinary, supplemental O₂therapy, etc.; (k) unique calibration methodology; (l) quantifiablecolorimetric CO₂ concentration monitoring at respiratory rates up to atleast 40 BPM; (m) various patient attachment configurations andembodiments; (n) custom data display presentation; (o) wireless(Bluetooth) data connectivity to tablet computer or smart phone; (p) noroutine maintenance of electronic module-indicator has 3 year shelflife; and (r) potential for revenue from disposable indicator that isreplaced daily.

Methods of Quantitative Colorimetric CO₂ Measurement

Additional embodiments are directed to methods for measuring a componentof a patient's breath (e.g. carbon dioxide) using a quantitativecolorimetric device or system such as those described herein. Forexample, referring generally to FIGS. 1-2 , a patient may exhale into aninlet 102 of a quantitative colorimetric device. The inlet 102 maydirect the entire breath sample or a portion of the exhaled air into anindicator compartment, unit, or testing chamber 115. The indicator unit115 can include a colorimetric indicator 116 positioned for exposure tothe breath sample. Once exposed to the breath sample, the indicatorchanges colors from a baseline color. The color change is based on theconcentration of a component (e.g. carbon dioxide) in the breath sample.

Once the breath sample has been introduced into the measurement device,an electro-optical assembly transmits a reference light to a surface ofthe indicator. Light reflected back from the surface of the indicator isdetected by a photodetector in the electro-optical assembly. Thephotodetector generates an electrical signal based on the reflectedlight. The electrical signal is then transmitted to a processor orcomputer for analysis, such as signal processing, to determine if acolor change has occurred and the concentration of the gas component inthe breath sample based on any color change. Additionally, the processormay refer to calibration data or a calibration curve for the system incomputing the concentration of the gas component in the breath sample.The calibration data may be stored in the processor or elsewhere on thesystem. For example, each indicator unit may have its own particularcalibration data. As such, each indicator unit may include storedcalibration data that can be accessed by the processor for quantitativegas concentration calculations. The calibration data may be stored in aflash memory device on the indicator unit.

Once the gas component concentration is determined, the concentrationmay be displayed on a monitor. The quantitative colorimetric system mayinclude a display monitor or, alternatively, the system may communicatethe information to a remote monitor through a wired or wirelessconnection. The display can be a mobile display device, such as asmartphone or tablet, or a non-mobile display device, such as atelevision.

Any measurements for a patient may be stored locally on the device orremotely for later retrieval. This allows the patient as well as medicalprofessionals to monitor the tested component's levels in the patient'sbreath.

In some embodiments, a measuring session includes one or more of thefollowing steps:

-   -   (a) Attaching a fresh indicator assembly or unit to the sensor        assembly    -   (b) Turning on the electronics module power button (or otherwise        activating the electronics module)    -   (c) Calibrating the measurement system such as by automatically        conducting a span calibration by having the sensor “read” the        signal from the color associated with a known CO₂ concentration.        (e.g. electronics module performs calibration)    -   (d) Removing a calibration ampoule from the indicator assembly        or unit    -   (e) Performing a zero calibration (e.g. the electronic module        may automatically performs a zero calibration in room air,        assumed to be zero CO2)    -   (f) Attaching an indicator/sensor assembly and/or a sample tube        to the patient (such as attaching to the nose alar)    -   (g) Instructing the user to begin breathing    -   (h) Recording the testing session (e.g. the electronics module        may automatically record the test session)    -   (i) Measuring real-time breath-by-breath gas component        concentrations (e.g. partial pressure and/or volume percent)    -   (j) Computing real time, time varying gas component (e.g. CO₂)        waveforms.    -   (k) Computing respiratory rate    -   (l) Monitoring patient parameters    -   (m) Computing end tidal CO₂ concentrations if applicable    -   (n) Alerting the user if it detects any measurement errors or        artifacts in the measurement process (e.g. electronics module        alerts user).    -   (o) Electronically transmitting data to a remote smartphone,        tablet or other internet connected device for subsequent        storage, retrieval, sharing and healthcare provider analysis        (e.g. wireless or wired transmission).    -   (p) Prompting the user for certain breathing rate and breathing        depth patterns, alerts, instructions, session time and error        messages such as “replace indicator”, “wireless disconnect” or        other malfunctions (e.g. mobile device may perform prompting)        Methods for Breathing Therapy

In addition to the above, various aspects of the inventions are directedto a breathing therapy system for non-invasively andnon-pharmaceutically treating various conditions include panic disorder,anxiety, general anxiety disorder, obsessive-compulsive disorder, socialphobia, depression, apnea, migraines, epilepsy, asthma, post-traumaticstress disorder, and hypertension. Some embodiments described herein aredirected toward breathing therapy to treat a disorder or disease. Forexample, quantitative colorimetric carbon dioxide detection systemdescribed can be used to measure and modify a user's CO₂ levels toprovide treatment for any number of disorders or illnesses.

In some cases, a patient's end-tidal CO₂ levels are monitored and/ormodified. Generally, end-tidal CO₂ refers to the carbon dioxide levelsmeasured in a user's exhaled airflow. FIG. 14 provides a generalrepresentation of the expiration and inspiration pattern for respirationwhere end-tidal CO₂ is measured at the peak 50 of expiration. End-tidalCO₂ levels can be measured in partial pressure units such as mmHg.Additionally, CO₂ levels in general, including end-tidal CO₂, can bequantitatively measured in terms of concentration. Concentration may bemeasured in volume percent or pressure. In some embodiments, the carbondioxide values may be measured in one unit and converted to another. Forexample, partial pressure values may be derived from measuredconcentration percentages. In further variations, the carbon dioxidevalues may be measured in pressure values directly.

As can be appreciated, measuring and modifying end-tidal CO₂ levels maybe described as a non-limiting example of one treatment application forthe quantitative colorimetric gas component detection systems described.CO₂ levels measured may include (but is not limited to) end-tidal CO₂.Similarly, CO₂ may be quantified in terms of partial pressure units(e.g. mmHg) as illustrated in examples described. However, it is to beunderstood that any units may be used to quantify the amount of CO₂measured from a gas sample (including volume percentage) for thepurposes of this disclosure.

As described, some embodiments contemplated provide for a breathingtherapy system having a device for measuring the concentration ofcomponents in a user's exhaled air. The device may display the measuredcomponents in any suitable units including pressure units. The devicemay include sensors for measuring CO₂ levels in the expired air as wellas sensors for measuring other parameters of the user such as breathingrate, pulse rate, blood oxygen saturation level, etc.

For illustration purposes, FIG. 15 shows a general quantitativecolorimetric capnometer having a main sensing unit 1522 and a connector1524. The main sensing unit 1522 may include any of the componentsdescribed such as a colorimetric indicator and an electro-opticalsensing assembly. In some embodiments, the breathing system 1520 mayfurther include a display component 1526 for providing measuredend-tidal CO₂ levels, breathing rate, or any other measured/sensed userinformation. The display component 1526 may provide numerical values forthe measured/sensed information and/or provide a graph showing theuser's respiration patterns.

Referring again to FIG. 15 , some embodiments provide for CO₂ measuringdevices that record measured parameters during use. The device, such asa quantitative colorimetric capnometer or an IR absorption spectroscopysidestream capnometer, may record the information locally within thedevice for later retrieval by the user or a medical professional. Inother embodiments, the capnometer may communicate the user's informationthrough a wired or wireless connection to a centralized database. Thecapnometer may electronically communicate the user's information to amobile device such as a smart phone, tablet, laptop, etc. In such cases,the mobile device 1526 may electronically receive the user'sinformation, process the information, and provide the user andclinician/caregiver with a summary or assessment of the user's progress.

In further embodiments, the capnometer may communicate the user'sinformation to the mobile device 1526 during a patient's use. The mobiledevice 1526 processes the information in real-time or dynamically toprovide the user with a graphical representation of respiratory gasexchange parameters. FIG. 16 shows graphical representation of a user'send-tidal carbon dioxide levels and breathing rate per minute duringcapnometer use. The mobile device 1526 can receive user information fromthe capnometer and display such information during use (and/or afteruse). Alternatively, in some embodiments, the patient's respirationinformation is measured but not displayed.

To provide breathing therapy, the quantitative colorimetric devicesdescribed may include a stored breathing therapy protocol or treatmentprogram that is executed while the patient provides breath samples. Forexample, the system or device may include a processor with a storedbreathing protocol that activates based on the concentration or pressureof end-tidal CO₂ measured in the patient's breath sample. The programmay use visual or audio cues to guide the patient to a target breathingrate and/or CO₂ concentration/pressure. The visual or audio informationor cues may be presented to the user through a display screen and/oraudio device such as headphones. In some cases, the patient attachmentwould include a microphone allowing the user to record audible comments(time stamped) during the therapy session thus eliminating the need formanual note taking. As described above, the display screen or audiodevice may be integrated with the measuring components. (See FIGS.10-13B).

As an example, some embodiments described provide for breathingtherapies, methods, systems and devices that treat a disorder or illnessby helping a user modify end-tidal CO₂ levels in exhaled air. Forexample, a user may be guided either visually or audibly to attain ormaintain target end-tidal CO₂ levels in exhaled breath. In some cases,the desired target end-tidal CO₂ level is between about 37 mmHg andabout 43 mmHg.

End-tidal CO₂ modification can be accomplished in several ways accordingto the described embodiments. For example, as shown in FIG. 17 , someembodiments provide for a three-stage therapy for modifying end-tidalCO₂. In such embodiments, the first stage can be a baseline stage 1700where the patient's baseline data is collected. In some cases, the firststage lasts about two minutes. A second stage may be a pacing stage 1702during which the patient is instructed on how to modify breathingpatterns. The pacing stage may include instructions to adjust breathingrate, exhalation length, inhalation length, volume of air intake forinhalation; and/or target carbon dioxide levels. The pacing stage may bedesigned based on the patient's baseline data. In some cases, the secondstage lasts about ten minutes or less. Following the second stage, athird stage may be used to help patients practice pacing methods. Forexample, the patient may attempt to maintain a breathing pattern withoutinstructions or cues available in the second stage. In some cases, thepatient may refer to biofeedback to help the patient maintain a targetbreathing pattern in the third stage. Biofeedback can include monitoringcarbon dioxide levels and respiratory rate. In some embodiments, thethird stage is a transition stage 1704 that lasts about five minutes orless. Additional details for each of the three stages are provided inthe following sections.

During the baseline stage, the patient may sit quietly and breathenormally with eyes closed. Patient data may be collected to show thepatient's respiration parameters prior to any instruction ormodification. The patient's respiration parameters may be measuredand/or recorded by a capnometer or a breathing therapy system as shownin FIGS. 1-13B and 15 . Additionally, other patient parameters (e.g.oxygen saturation, blood pressure, heart rate, etc.) may be measured ormonitored during the baseline stage. In some cases, the baseline stagemay last two-minutes. In other embodiments, the baseline stage may beshorter or longer as needed to adequately collect the patient'spre-instruction and pre-modification parameters.

The user's information may be stored and/or electronically communicatedfrom a capnometer to a central database or to a mobile device. In othercases, a therapist may be on-site to receive the collected data. Wherethe capnometer communicates the user's data to a central database ormobile device, the database or mobile device may perform an algorithm toassess an appropriate breathing therapy for the user. For example, ifthe user's end-tidal CO₂ levels are measured to be below a desiredtarget range, the algorithm may provide instructions that the usershould increase end-tidal CO₂ through breathing exercises. If a user hasa breathing rate of 16 breaths per minute (bpm), the algorithm mayprovide instructions that the user should reduce breathing rate. Inother embodiments, the instructions may request that the user adjustbreathing rate to match a target rate.

Once the appropriate therapy is determined by the algorithm or by atherapist, the patient enters the second stage or pacing stage. In someembodiments, the pacing stage provides for visual or audio guidance tohelp the patient modify breathing patterns, habits, and end-tidal CO₂.For example, in some embodiments where a mobile device is used, themobile device may play a set of audio tones, visual cues, pacing tones,audible instructions or music to guide the patient's cyclic rhythm ofinspiration and expiration.

The audio tones may help the patient pace his breathing with targetbreathing patterns. For example, the audio tones may increase in volumeor pitch to indicate inspiration and lower in volume or pitch toindicate expiration. Moreover, the duration of the audio tones duringinspiration may be shorter than the audio tones during expiration orvice versa to indicate the length of inhalation and exhalation. In someembodiments, rising tones indicate inspirations and falling tonesindicate expiration. In other embodiments, the audio tones or tonepatterns include silence which indicates a pause between exhalation andinhalation or inhalation and exhalation.

Additionally, the breathing cues may guide the patient to a modifiedrespiratory rate. Because a patient may present with a higher breathingrate to start, embodiments described provide exercises to graduallyreduce breaths per minute to a target range. For example, during thebaseline stage, the patient may present with 15 bpm (breaths perminute). The capnometer collects this information and communicates thedata to a mobile device. The mobile device receives the user data duringthe baseline stage and operates an appropriate therapy protocol in thepacing stage step. The therapy protocol (or second stage) may entail aten-minute period during which the patient breathes along with pacing oraudio tones (e.g. tone patterns) to guide them in their breaths perminute.

In some embodiments, tones patterns guide the patient to adjust hisbreaths per minute to 13 bpm, 11 bpm, 9 bpm, or 6 bpm, etc. Although 13,11, 9, 6 breaths per minute are given as examples, it can be appreciatedthat depending on a patient's baseline, modifications of the pacingtones may be required. For example, the tone pattern can be modulated tocorrespond to a respiration rate of 13 breaths per minute in a firsttherapy session and to rates of 11, 9, and 6 breaths per minute insuccessive sessions. However, if the patient's baseline is 13 bpm, thenthe treatment may begin with tone patterns for 11 bpm. In other cases,it may be desirable to use 15, 12, 10, 8, and 6 bpm patterns. In anotherexample, the patient's breath may be below a target bpm. The tonepatterns may guide the patient to increase bpm. In some embodiments thetherapy guides the patient to a respiration rate of about 6 bpm to about13 bpm.

Additionally, in some variations, the breathing cues will instruct theuser to adjust volume of inhaled air to match a target volume. In somecases, the user will be instructed to reduce volume of inhaled air. Theuser may be taught how to breathe air such that the volume of air is ator near a target level. In some cases, reducing the volume of inhaledair can be used to treatment a disorder, condition, and/or disease.Additionally, one way to measure the volume of air in a breath is bymeasuring the end-tidal CO₂ levels.

Visual breathing guidance may be used in combination or alone forguiding the user's breathing pattern. For example, colors, lines,shapes, words, letters, pictures, etc. may be used to indicate length ofinhalation or exhalation and pauses in between. Moreover, visual cuesmay be used to teach the user how to attain or maintain desiredend-tidal CO₂ levels, respiratory rate, etc. For example, a graphmeasuring end-tidal CO₂ levels may be shown to encourage the user toattain or maintain a target level of end-tidal CO₂.

As described, instructing the user to modify breathing pattern may leadto increased end-tidal CO₂ levels. In some embodiments, the end-tidalCO₂ levels are increased or maintained at about 37 mmHg to about 43 mmHgby decreasing to or maintaining breaths per minute at about 6 bpm.

Upon completion of one or more pacing stages, the patient may enter atransition stage. The transition stage allows the patient to practicethe breathing patterns used in the pacing stage without any outsideguidance. However, alternatively, the pacing tones and visual/audio cuesmay also be provided during the transition stage depending on thepatient's needs. In some cases, even where the breathing cues areprovided, the patient may be instructed not to follow or rely upon thecues.

Additionally, in the transition stage, the patient may regularly orsporadically check his measured parameters including end-tidal CO₂levels and respiratory rate to monitor progress. Patients may also beencouraged to attain or maintain target breathing rate and end-tidal CO₂levels by monitoring measured parameters.

In some embodiments, the treatment described takes places over thecourse of four weeks. The three-stage exercise (baseline, pacing, andtransition) may be repeated two or more times every day for multipleweeks. In some cases, the three-stage exercise is performed for one weekor more, including four weeks. Each week the pacing stage may be alteredbased on the patient's progress. For example, if the patient hasachieved a 9 bpm breathing rate, the pacing stage protocol may bechanged to guide the patient to a 6 bpm breathing rate. Generally, thepacing stage will change each week. However, it can be appreciated thatdepending on the patient's progress, the treatment timeline may bemodified accordingly. In some embodiments, the baseline duration may beabout two minutes, the pacing duration about ten minutes, and thetransition duration about five minutes.

In further embodiments, the tone patterns or breathing therapy mayinclude techniques from (1) Capnometry Assisted Respiratory Therapy(CART). A therapy protocol developed by Meuret, A. E., Wilhelm, F. H.and Roth, W. T. as described in the paper “RespiratoryBiofeedback-Assisted Therapy in Panic Disorder,” published in BehaviorModification September 2001), issue 25, pages 584-605; (2) TargetingpCO2 in Asthma: Pilot Evaluation of a Capnometry-Assisted BreathingTraining Alicia E. Meuret, Thomas Ritz, Frank H. Wilhelm, Walton T. RothAppl Psychophysiol Biofeedback (2007) 32:99-109; and (3) the ButeykoMethod which are herein incorporated by reference in their entirety.

As described, in some embodiments, the breathing therapy treatment maybe executed by a system utilizing software (e.g. mobile app) that can bedownloaded to a patient's personal computing device. For example,software for the therapy can be downloaded and executed on a mobiledevice that electronically communicates with a capnometer. The softwareor program may provide for immediate breathing feedback to the patientthrough audio guidance and visual displays, allowing the patient toadjust his or her respiration rate and end-tidal CO₂ levels. Thesoftware or program may store training sessions and training sessionresults for review by a medical professional or the patient.

The program may display a graph showing the end-tidal CO₂ levels andbreathing rate with goal lines for target values. FIG. 16 shows goalline (dashed) CO₂ pressure at 40 mmHg and goal line (dashed) 13 bpm forbreathing rate. In some embodiments, the system may provide the patientwith advice or tips during the session on how to reach goals such asraising end-tidal CO₂. As shown in FIG. 16 , current CO₂ levels areindicated in a blue box that shows the CO₂ level of the patient's lastbreath. The blue line leading up to the blue box shows a record of thepatient's CO₂ level during the current breathing session. The white boxnext to the Current CO₂ level shows the Target CO₂ level, which is 37-40mmHg (“millimeters of Mercury”) in the example. The number in the greenbox shows the current Respiration Rate (RR). The green line leading upto the green box shows a record of the patient's RR during the currentbreathing session. The white box next to the Current Respiration Rateshows the Target Respiration Rate.

In further embodiments, the system may alert the user if breathing rateor end-tidal CO₂ levels exceed a safety limit, which may include beingabove or below a safety limit. The system may also alert the user if thecapnometer has become disconnected from the system. The graphicalrepresentation may also include icons showing the operability of thecapnometer device including icons for battery use, sensor activation,and Bluetooth connectivity. The graphical representation may alsoinclude graphical user interface components for the user to manipulate(e.g. click) to receive breathing therapy instructions.

In further embodiments, the program may include a calibration protocolto prepare the device for measuring a patient's breath. In some cases,the program or software may automatically calibrate the system asdescribed above (e.g. span and zero calibration). In other cases, thecalibration software may calibrate based on ambient air in the patient'senvironment. Additionally, the program or software may use GPS todetermine the altitude of the patient's location. Altitude may befactored into the patient's breathing therapy. For example, thecalculation for CO₂ level may take into account barometric pressure.Altitude can be used to calculate (and get a close approximation) ofbarometric pressure.

Additionally, during treatment, the patient can view breathing rate,end-tidal CO₂ levels, or any other collected data/parameters forfeedback and guidance on progress. The patient can use the display onthe capnometer or on a connected mobile device to track progress. Insome embodiments, the visual or audio cues for breathing patternlearning, capnometer, display, and any other components for treatmentare contained in a single device. The device may include a processor forexecuting a pre-programmed treatment session. The processor may alsoelectronically receive measurements from the capnometer for processingor display.

In further embodiments, the methods, systems, and devices described maybe applicable to: (a) Preventative and self-directed healthcare(complies with ACA); (b) Home-based biofeedback for Panic Disorder,PTSD; (c) Assessment of asthma medication efficacy; (d) Pre hospital,triage, paramedic/EMT intubation verification; (e) Buteyko methodtraining monitoring for asthma related self-therapy; (f) Supplemental O₂home therapy-demand valve triggering for gas consumption reduction; (g)Home-based sleep studies, nasal CPAP, neonatal sleep apnea monitoring;(h) Conscious sedation procedures (outpatient surgery, colonoscopies,eye surgery, oral surgery, etc.); (i) Dental office procedures and oralsurgery; (j) MRI radiology procedure monitoring—with employmentnon-interfering fiber optic indicator; (k) Self-controlled analgesiamonitoring for pain management; and (l) Third world clinics and surgicalcenters.

As for additional details pertinent to the present invention, materialsand manufacturing techniques may be employed as within the level ofthose with skill in the relevant art. The same may hold true withrespect to method-based aspects of the invention in terms of additionalacts commonly or logically employed. Also, it is contemplated that anyoptional feature of the inventive variations described may be set forthand claimed independently, or in combination with any one or more of thefeatures described herein. Likewise, reference to a singular item,includes the possibility that there are plural of the same itemspresent. More specifically, as used herein and in the appended claims,the singular forms “a,” “and,” “said,” and “the” include pluralreferents unless the context clearly dictates otherwise. It is furthernoted that the claims may be drafted to exclude any optional element. Assuch, this statement is intended to serve as antecedent basis for use ofsuch exclusive terminology as “solely,” “only” and the like inconnection with the recitation of claim elements, or use of a “negative”limitation. Unless defined otherwise herein, all technical andscientific terms used herein have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. The breadth of the present invention is not to be limited bythe subject specification, but rather only by the plain meaning of theclaim terms employed.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical rangerecited herein is intended to include all sub-ranges subsumed therein.

What is claimed is:
 1. A breathing therapy method comprising: receivingat least a portion of a user's exhaled air in a gas inlet of aquantitative colorimetric detection system; measuring a user's end-tidalCO₂ levels with the quantitative colorimetric detection system based ona color change resulting from exposure of the system to the user'sexhaled air; controlling a temperature of a colorimetric indicator inthe quantitative colorimetric detection system while measuring theuser's end-tidal CO₂ levels and outputting a set of visual and/or audiocues from the quantitative colorimetric system with instructions for theuser to adjust their breathing pattern to coincide with the cues tothereby modify the user's exhaled end-tidal CO₂ levels to between about37 mmHg and 43 mmHg.
 2. The method of claim 1, wherein the breathingpattern includes the exhaled CO₂ level and respiration rate.
 3. Themethod of claim 1, further comprising displaying the user's measured CO₂levels to provide visual feedback during treatment.
 4. The method ofclaim 1, further comprising displaying the user's breathing rate toprovide visual feedback during treatment.
 5. The method of claim 1,wherein the outputting step comprises outputting a set of timed toneshaving an audible sequence of rising tones, falling tones, and silence.6. The method of claim 5, wherein the rising tones indicate inspiration,falling tones indicate expiration, and silence indicates a pause in theuser's respiration, the method further comprising the user breathing inat the rising tones, breathing out at the falling tones and notbreathing during silent periods.
 7. The method of claim 1, furthercomprising measuring a baseline CO₂ level for the user prior tomodification.
 8. The method of claim 1, further comprising treatingpost-traumatic stress disorder (PTSD), panic disorder, anxiety, asthma,hypertension, obsessive-compulsive disorder, social phobia, depression,apnea, migraines, or epilepsy by training the user to modify theirexhaled CO₂ levels.
 9. The method of claim 1, further comprisingmeasuring a temperature of a colorimetric indicator in the quantitativecolorimetric detection system while measuring the user's end-tidal CO₂levels and applying a temperature correction to the measured colorchange.